DELPHI: De-escalation of adjuvant radio(chemo)therapy for HPV(+) oropharyngeal SCC. A phase I personalization trial to reduce late toxicity

Summary of the Project

Standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) is surgery followed by radio- or radiochemotherapy dependent on clinical risk factors. Patients with HPV16(+) HNSCC show higher tumor cure rates after primary radiochemotherapy than HPV(-) tumors. This applies also for postoperative radiochemotherapy with >95% cure rates 5 years after treatment.

While HPV(+) HNSCC patients are young, severe late toxicity is frequent after multimodal treatment with 21% and 42% at 3 and 5 years. As late toxicity correlate with radiation dose at organs at risk, a dose reduction in HPV(+) HNSCC appears promising to reduce toxicity and is justified in view of the high locoregional control rates.

The approach of a controlled stepwise reduction of radiation doses has been successfully applied in the past in low-risk Hodgkin lymphoma patients, where the lower radiation doses were finally demonstrated as superior to higher doses with similar cure but lower late toxicity rates. A similar concept is planned in the present trial with the present phase I trial being the first step.

If the hypothesis can be verified, a randomized trial will be performed using the lowest effective radiation dose defined in this trial. This randomized trial would need to test the hypothesis that the lower radiation dose leads to lower late toxicity while efficacy stays constant.

Scientific Goals

show safety of reduced-dose adjuvant radiochemotherapy

show reduced late toxicity after reduced-dose adjuvant radiochemotherapy